Week 3 Flashcards
What chromosomal abnormality is commonly associated with testicular germ cell tumors? What gene is overexpressed in this abnormality?
Isochromosome 12p, in which the short arm of chromosome 12 is duplicated, is commonly associated with testicular germ cell tumors. Cyclin D2, which is found on the short arm of chromosome 12, is overexpressed, leading to rapid cell growth and division.
What are some serum markers associated with testicular germ cell tumors? What tumors are they associated with, and what are their half-lives?
ß-hCG: produced by syncytiotrophoblasts, seen in both seminomas and non-seminomatous germ cell tumors; can be massively elevated in choriocarcinoma; half-life 24-36 hours
⍺-fetoprotein: produced by yolk sac elements; indicative of a yolk sac tumor, never seen in a pure seminoma; half-life 5-7 days
LDH: Especially seen in seminomas, but can be produced by any testicular tumor; suggestive of tumor burden; half-life 10 hours-3 days
What lymph nodes do the testes drain to? What lymph nodes does the scrotal skin drain to? What is the clinical significance of this difference?
The testes drain to the retroperitoneal lymph nodes, with the right testis draining to the interaortocaval nodes and the left testis draining to the para-aortic and left hilar nodes. The scrotal skin, being a component of the body wall, drains to the superficial inguinal lymph nodes. As a consequence of this difference, clinicians must be careful to avoid seeding the scrotal lymphatics in patients with testicular cancer, as this can cause more widespread metastasis of the tumor. Practically, this means that testicular tumors are rarely biopsied, and orchiectomies are performed via an inguinal rather than scrotal approach.
What form of sexual dysfunction is a potential complication in a man who has undergone a retroperitoneal lymph node dissection?
a. Reduced penile sensation
b. Erectile dysfunction
c. Priapism (persistent erection)
d. Ejaculatory dysfunction
e. Painful orgasm
The correct answer is d, ejaculatory dysfunction. When performing a retroperitoneal lymph node dissection, there is a risk of damaging the lumbar splanchnic nerves. These nerves provide sympathetic innervation to the pelvic viscera, which is necessary for ejaculation. Thus, a potential complication of a RPLND is an inability to ejaculate.
For spermatogenesis to take place, the concentration of testosterone within the seminiferous tubules must be kept high. How is this accomplished?
The Sertoli cells produce a peptide, antigen-binding protein, that binds and concentrates testosterone within the seminiferous tubules.
A worker at an in vitro fertilization clinic is attempting to fertilize isolated oocytes by incubating them with fresh sperm obtained from a donor. However, despite prolonged incubation, fertilization does not occur. The sperm display normal morphology and motility. What might explain the inability of these sperm to fertilize?
In order for sperm to be capable of fertilization, they must undergo a process known as capacitation, in which a variety of biochemical changes, including surface glycoprotein cleavage and an increase in intracellular cAMP concentration, take place. During unassisted conception, this occurs in the female reproductive tract. In in vitro fertilization, the sperm must first be treated with a chemically defined medium in order to induce capacitation prior to oocyte incubation.
Which neurotransmitter is associated with increased sexual desire? Which neurotransmitter is associated with decreased sexual desire?
Dopamine is associated with increased sexual desire, while serotonin is associated with reduced sexual desire; this explains why one side effect of antidepressants that function through serotonin reuptake inhibition is reduced libido.
What are the three categories of pelvic floor disorders, and what are common factors associated with their development?
The three categories are pelvic organ prolapse, urinary incontinence, and fecal incontinence. Risk factors for all three conditions include childbirth, aging tissue, and positive family history.
What are important questions to ask a patient presenting with erectile dysfunction? What are potential ED treatment options?
In any patient with erectile dysfunction, it is important to differentiate between organic and psychogenic etiologies. This can be done by asking if the patient experiences erections in situations outside of partnered sexual activity. If so, then it is more likely that the ED has a psychogenic origin. If not, then organic diseases, such as dyslipidemia, hypertension, and diabetes mellitus should be considered. Other important questions include ascertaining the severity and duration of the dysfunction as well as determining whether any other components of the sexual response (e.g., desire, orgasm) are impaired.
First-line treatment options for ED include behavioral changes and PDE-5 inhibitors like sildenafil and tadalafil. In cases of organic disease, treating the underlying condition may also help to alleviate ED symptoms. If these interventions fail, invasive therapies like intracavernosal injections, transurethral pellets, vacuum erection devices, and penile prostheses may be considered.
What are the three most common types of renal cell carcinoma? How do they compare in terms of prevalence and prognosis?
The three most common types are clear cell carcinoma, papillary carcinoma, and chromophobe carcinoma.
Prevalence (most common to least common):
Clear cell > Papillary > Chromophobe
Prognosis (most favorable to least favorable):
Chromophobe > Papillary > Clear Cell
The prognosis for clear cell and papillary carcinomas can be further stratified based on their histologic appearance (Fuhrman grade for clear cell carcinoma and Type 1 vs. Type 2 for papillary carcinoma)
How is renal cell carcinoma managed? How does management differ between localized and metastatic disease?
Localized Disease:
Radical nephrectomy or, in certain cases, partial nephrectomy is the most common form of management. In the case of small tumors, cryoablation/radiofrequency ablation or even observation/surveillance may be considered.
Metastatic Disease:
In the case of disease that has spread into the IVC/right atrium, surgical resection is possible. For widespread/systemic metastases, immunotherapy, particularly with IL-2, is the standard approach; notably, conventional cytotoxic chemotherapy is generally not used. More recently developed therapeutics include anti-VEGF antibodies, multifunctional tyrosine kinase inhibitors (e.g., sorafenib), mTOR inhibitors, and immune checkpoint inhibitors.
How do low-grade and high-grade urothelial malignancies of the bladder differ in terms of their genetic makeup, clinical manifestation, and management?
Genetic Makeup:
Low-Grade: Most common chromosomal abnormality is loss of the long arm of chromosome 9 (9q); gives rise to a proliferative phenotype
High-Grade: Generally displays mutations in p53 that give rise to a dysplastic phenotype
Clinical Manifestation:
Low-Grade: Restricted to the superficial bladder lining; does not invade past the tunica muscularis propria
High-Grade: Invades the bladder wall beyond the tunica muscularis propria
Management:
Low-Grade: Treated with transurethral resection of the bladder tumor (TURBT) and periprocedural mitomycin followed by topical immunotherapy with intravesical BCG
High-Grade: Treated with neoadjuvant systemic chemotherapy followed by radical cystectomy, extended pelvic lymph node dissection, and urinary reconstruction
Why are serum PSA levels elevated in prostate cancer? What other conditions can also produce this elevation?
PSA is a peptide produced by the prostatic acinar cells that is secreted in a polar fashion into the prostatic duct system. In prostate cancer, the normal polar orientation of the acinar cells is disrupted, enabling the secretion of PSA into the surrounding vasculature, thus raising serum levels. Other conditions that can result in an increased serum PSA include prostatitis and benign prostatic hyperplasia.
What are the different zones of the prostate? How do they differ in terms of the pathology that affects them?
Peripheral zone: Comprises most of the volume of the prostate; contains of most of the prostatic acini and is thus the location where most prostate cancers originate
Central zone: About 25% of the prostate volume; gives rise to 5-10% of prostate cancers
Transition zone: Periuretheral zone, involved in 10-20% of prostate cancers; more commonly involved in benign prostatic hyperplasia; notably, BPH is not considered a risk factor for the subsequent development of prostate cancer
How is localized penile cancer typically managed? How does this differ from the management of invasive penile cancer?
Penile cancer that is limited to intraepithelial neoplasia can often be managed with organ-sparing approaches, including circumcision if the foreskin is affected, Mohs surgery, and topical 5-fluorouracil therapy. In contrast, invasive penile cancer generally requires partial or total penectomy with a subsequent bilateral inguinal lymph node dissection.
